ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Parasite-derived arginase influences secondary anti-Leishmania immunity by regulating programmed cell death-1-mediated CD4+ T cell exhaustion.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Review
- Long pentraxin 3 (PTX3) regulates IL-17A-mediated immunity toFrontiers in immunology · 2026Article
- Combined anti-PD-1 and amphotericin B therapy reduces fungal burden and enhances control of murine paracoccidioidomycosis.Frontiers in cellular and infection microbiology · 2026Article
- A molecular signature for IL-10-producing Th1 cells in protozoan parasitic diseases.JCI insight · 2023Article
- New Immunological Markers in Chromoblastomycosis-The Importance of PD-1 and PD-L1 Molecules in Human Infection.Journal of fungi (Basel, Switzerland) · 2023Article
- Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?Frontiers in immunology · 2022Review
- Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis.The Journal of clinical investigation · 2021Article
- Article
- A proportion of CD4+ T cells from patients with chronic Chagas disease undergo a dysfunctional process, which is partially reversed by benznidazole treatment.PLoS neglected tropical diseases · 2021Article
- PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis.Frontiers in immunology · 2021Article
- Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism.Cytokine: X · 2020Article
- The Role of PD-1 in Acute and Chronic Infection.Frontiers in immunology · 2020Review
- Immunotherapy using anti-PD-1 and anti-PD-L1 in Leishmania amazonensis-infected BALB/c mice reduce parasite load.Scientific reports · 2019Article
- STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles.Scientific reports · 2018Article
- Immune checkpoint blockade in infectious diseases.Nature reviews. Immunology · 2018Review
- Centrin-DeletedFrontiers in immunology · 2018Article
- Phenotypic and Functional Profiles of Antigen-Specific CD4Frontiers in cellular and infection microbiology · 2018Article
- Leptin regulates Granzyme-A, PD-1 and CTLA-4 expression in T cell to control visceral leishmaniasis in BALB/c Mice.Scientific reports · 2017Article
- HIF-1α is a key regulator in potentiating suppressor activity and limiting the microbicidal capacity of MDSC-like cells during visceral leishmaniasis.PLoS pathogens · 2017Article
- Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites.PLoS neglected tropical diseases · 2017Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The breakdown of L-arginine to ornithine and urea by host arginase supports Leishmania proliferation in macrophages. Studies using arginase-null mutants show that Leishmania-derived arginase plays an important role in disease pathogenesis. We investigated the role of parasite-derived arginase in secondary (memory) anti-Leishmania immunity in the resistant C57BL/6 mice. We found that C57BL/6 mice infected with arginase-deficient (arg(-)) L. major failed to completely resolve their lesion and maintained chronic pathology after 16 wk, a time when the lesion induced by wild-type L. major is completely resolved. This chronic disease was associated with impaired Ag-specific proliferation and IFN-γ production, a concomitant increase in programmed cell death-1 (PD-1) expression on CD4(+) T cells, and failure to induce protection against secondary L. major challenge. Treatment with anti-PD-1 mAb restored T cell proliferation and IFN-γ production in vitro and led to complete resolution of chronic lesion in arg(-) L. major-infected mice. These results show that infection with arg(-) L. major results in chronic disease due in part to PD-1-mediated clonal exhaustion of T cells, suggesting that parasite-derived arginase contributes to the overall quality of the host immune response and subsequent disease outcome in L. major-infected mice. They also indicate that persistent parasites alone do not regulate the quality of secondary anti-Leishmania immunity in mice and that the quality of the primary immune response may be playing a hitherto unrecognized dominant role in this process.
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